Jia Jian, Tao Xu, Tian Zhouning, Liu Jing, Ye Xiaoman, Zhan Yiyang
Department of General Practice, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Department of Geriatric Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Exp Ther Med. 2022 Apr;23(4):314. doi: 10.3892/etm.2022.11243. Epub 2022 Mar 1.
The vitamin D receptor (VDR) may regulate blood pressure via multiple pathways. The present study investigated the underlying mechanism by which deficiency increases blood pressure. A total of 16 8-week-old male littermate mice were randomly divided into the knockout and wild-type groups ( and , respectively). Blood pressure was measured using a four-channel PowerLab data acquisition and ADI software analysis system. After euthanasia, vascular smooth muscle cells (VSMCs) were isolated from the and mice. Oxidative stress, renin-angiotensin system () activation and autophagy markers were measured in the isolated VSMCs using reverse transcription-quantitative PCR (RT-qPCR), western blotting and transmission electron microscopy (TEM) assays. Mean systolic pressure was significantly higher in the mice compared with the mice. RT-qPCR and western blotting analyses indicated that RAS markers (angiotensin II and II type 1 receptor) were significantly upregulated, oxidative stress was increased (evidenced by reduced superoxide dismutase and peroxiredoxin-4) and autophagy was activated (upregulation of autophagy related protein 7, Beclin 1 and microtubule-associated proteins 1A/1B light chain 3A) in the VSMCs compared with the VSMCs. TEM demonstrated that there were more autophagy bodies in the VSMCs compared with the VSMCs. In conclusion, deficiency was associated with high blood pressure. The mechanism underlying the increase in blood pressure caused by deficiency may involve activation of the RAS, as well as increased oxidative stress and autophagy of VSMCs.
维生素D受体（VDR）可能通过多种途径调节血压。本研究调查了维生素D缺乏导致血压升高的潜在机制。总共16只8周龄的雄性同窝小鼠被随机分为基因敲除组和野生型组（分别为8只）。使用四通道PowerLab数据采集和ADI软件分析系统测量血压。安乐死后，从基因敲除小鼠和野生型小鼠中分离出血管平滑肌细胞（VSMC）。使用逆转录定量PCR（RT-qPCR）、蛋白质免疫印迹法和透射电子显微镜（TEM）检测法，在分离出的VSMC中测量氧化应激、肾素-血管紧张素系统（RAS）激活和自噬标志物。与野生型小鼠相比，基因敲除小鼠的平均收缩压显著更高。RT-qPCR和蛋白质免疫印迹分析表明，与野生型VSMC相比，基因敲除VSMC中的RAS标志物（血管紧张素II和1型受体）显著上调，氧化应激增加（超氧化物歧化酶和过氧化物还原酶-4减少证明），自噬被激活（自噬相关蛋白7、Beclin 1和微管相关蛋白1A/1B轻链3A上调）。TEM表明，与野生型VSMC相比，基因敲除VSMC中有更多自噬体。总之，维生素D缺乏与高血压有关。维生素D缺乏导致血压升高的潜在机制可能涉及RAS的激活，以及VSMC氧化应激和自噬增加。
